2ymk | pdb_00002ymk

Crystal structure of the hexameric anti-microbial peptide channel dermcidin

spinqualitylabelsall models 2ymk, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2ymk is a 3 chain structure with sequence from Homo sapiens. The June 2013 RCSB PDB Molecule of the Month feature on Dermcidin by David Goodsell is 10.2210/rcsb_pdb/mom_2013_6. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.49Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DCD_HUMAN DCD-1 displays antimicrobial activity thereby limiting skin infection by potential pathogens in the first few hours after bacterial colonization. Highly effective against E.coli, E.faecalis, S.aureus and C.albicans. Optimal pH and salt concentration resemble the conditions in sweat. Also exhibits proteolytic activity. Survival-promoting peptide promotes survival of neurons and displays phosphatase activity. It may bind IgG. Publication Abstract from PubMed Multicellular organisms fight bacterial and fungal infections by producing peptide-derived broad-spectrum antibiotics. These host-defense peptides compromise the integrity of microbial cell membranes and thus evade pathways by which bacteria develop rapid antibiotic resistance. Although more than 1,700 host-defense peptides have been identified, the structural and mechanistic basis of their action remains speculative. This impedes the desired rational development of these agents into next-generation antibiotics. We present the X-ray crystal structure as well as solid-state NMR spectroscopy, electrophysiology, and MD simulations of human dermcidin in membranes that reveal the antibiotic mechanism of this major human antimicrobial, found to suppress Staphylococcus aureus growth on the epidermal surface. Dermcidin forms an architecture of high-conductance transmembrane channels, composed of zinc-connected trimers of antiparallel helix pairs. Molecular dynamics simulations elucidate the unusual membrane permeation pathway for ions and show adjustment of the pore to various membranes. Our study unravels the comprehensive mechanism for the membrane-disruptive action of this mammalian host-defense peptide at atomistic level. The results may form a foundation for the structure-based design of peptide antibiotics. Crystal structure and functional mechanism of a human antimicrobial membrane channel.,Song C, Weichbrodt C, S Salnikov E, Dynowski M, O Forsberg B, Bechinger B, Steinem C, de Groot BL, Zachariae U, Zeth K Proc Natl Acad Sci U S A. 2013 Feb 20. PMID:23426625 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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